Membrane lipid remodeling eradicates Helicobacter pylori by manipulating the cholesteryl 6'-acylglucoside biosynthesis.

BACKGROUND: Helicobacter pylori, the main cause of various gastric diseases, infects approximately half of the human population. This pathogen is auxotrophic for cholesterol which it converts to various cholesteryl α-glucoside derivatives, including cholesteryl 6'-acyl α-glucoside (CAG). Since the related biosynthetic enzymes can be translocated to the host cells, the acyl chain of CAG likely comes from its precursor phosphatidylethanolamine (PE) in the host membranes. This work aims at examining how the acyl chain of CAG and PE inhibits the membrane functions, especially bacterial adhesion. METHODS: Eleven CAGs that differ in acyl chains were used to study the membrane properties of human gastric adenocarcinoma cells (AGS cells), including lipid rafts clustering (monitored by immunofluorescence with confocal microscopy) and lateral membrane fluidity (by the fluorescence recovery after photobleaching). Cell-based and mouse models were employed to study the degree of bacterial adhesion, the analyses of which were conducted by using flow cytometry and immunofluorescence staining, respectively. The lipidomes of H. pylori, AGS cells and H. pylori-AGS co-cultures were analyzed by Ultraperformance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) to examine the effect of PE(10:0)2, PE(18:0)2, PE(18:3)2, or PE(22:6)2 treatments. RESULTS: CAG10:0, CAG18:3 and CAG22:6 were found to cause the most adverse effect on the bacterial adhesion. Further LC-MS analysis indicated that the treatment of PE(10:0)2 resulted in dual effects to inhibit the bacterial adhesion, including the generation of CAG10:0 and significant changes in the membrane compositions. The initial (1 h) lipidome changes involved in the incorporation of 10:0 acyl chains into dihydro- and phytosphingosine derivatives and ceramides. In contrast, after 16 h, glycerophospholipids displayed obvious increase in their very long chain fatty acids, monounsaturated and polyunsaturated fatty acids that are considered to enhance membrane fluidity. CONCLUSIONS: The PE(10:0)2 treatment significantly reduced bacterial adhesion in both AGS cells and mouse models. Our approach of membrane remodeling has thus shown great promise as a new anti-H. pylori therapy.

Risk Factors for Pneumocystis jirovecii Pneumonia in Children With Systemic Lupus Erythematosus Exposed to Prolonged High-Dose Glucocorticoids.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in immunocompromised children with systemic lupus erythematosus (SLE). Prophylaxis against PJP in high-risk children is crucial, but the risk factors for PJP in children with SLE are not adequately characterized. This study sought to identify the risk factors for PJP in long-term glucocorticoid-treated pediatric SLE patients. METHODS: This study encompassed 71 treatment episodes involving 64 children with prolonged (≥4 weeks) high-dose (≥20 mg/d prednisone) steroid regimens. Fourteen treatment episodes involved the PJP, whereas others did not. Risk factors for PJP were assessed through Cox regression. The predictive value of these factors was evaluated using receiver operating characteristic curves. The incidence of PJP in different risk groups was compared using the Kaplan-Meier method. RESULTS: The creatinine (hazard ratio, 1.009; 95% confidence interval [CI], 1.001-1.017; p = 0.021) and the lowest lymphocyte count (hazard ratio, 0.007; 95% CI, 0.000-0.373; p = 0.014) were independent risk factors for PJP in children with SLE. The receiver operating characteristic curve showed that using creatinine greater than 72.5 µmol/L and the lowest lymphocyte count less than 0.6 × 109/L as risk predictors for PJP resulted in an area under the curve value of 0.934 (95% CI, 0.870-0.997; p < 0.001). The study revealed a significant increase in PJP prevalence (p < 0.001) in children with elevated creatinine levels and low lymphocyte count. CONCLUSIONS: Elevated levels of creatinine and decreased lymphocyte count are identified as distinct risk factors for PJP in children with SLE who receive prolonged high-dose steroid therapy.

Electroactive properties of EABs in response to long-term exposure to polystyrene microplastics/nanoplastics and the underlying adaptive mechanisms.

Given widespread presence of polystyrene (PS) microplastics/nanoplastics (MPs/NPs), the electroactive responses and adaptation mechanisms of electroactive biofilms (EABs) exposed long-term to PS-containing aquatic environments remain unclear. Therefore, this study investigated the impacts of PS MPs/NPs on electroactivity of EABs. Results found that EABs exhibited delayed formation upon initially exposure but displayed an increased maximum current density (Imax) after subsequent exposure for up to 55 days. Notably, EABs exposure to NH2PS NPs (EAB-NH2PSNPs) demonstrated a 50% higher Imax than the control, along with a 17.84% increase in viability and a 58.10% increase in biomass. The cytochrome c (c-Cyts) content in EAB-NH2PSNPs rose by 178.35%, benefiting the extracellular electron transfer (EET) of EABs. Moreover, bacterial community assembly indicated the relative abundance of electroactive bacteria increased to 87.56% in EAB-NH2PSNPs. The adaptability mechanisms of EABs under prolonged exposure to PS MPs/NPs predominantly operate by adjusting viability, EET, and bacterial community assembly, which were further confirmed a positive correlation with Imax through structural equation model. These findings provide deeper insights into long-term effects and mechanisms of MPs/NPs on the electroactive properties of EABs and even functional microorganisms in aquatic ecosystems.

Mechanistic insights into the response of electroactive biofilms to Cd2+ shock: bacterial viability and electron transfer behavior at the cellular and community levels.

Electroactive biofilms (EABs) play a crucial role in environmental bioremediation due to their excellent extracellular electron transfer (EET) capabilities. However, Cd2+ can have toxic effects on the electrochemical performance of EABs, and the comprehensive inhibition mechanism of EABs in response to Cd2+ shock remains elusive. This study indicated that Cd2+ shock significantly reduced biomass and increased oxidative stress in EABs at the cellular level. The bacterial viability of EABs in phase III under 0.5 mM Cd2+ shock (EABCd2+-III0.5) decreased by 16.31% compared to EABCK-III. Moreover, intracellular NADH, c-Cyts, and the abundance of electroactive species were essential indicators to evaluate EET behavior of EABs. In EABCd2+-III0.5, these indicators decreased by 26.32%, 33.40%, and 20.65%, respectively. Structural equation modeling analysis established quantitative correlations between core components and electrochemical activity at cellular and community levels. The correlation analysis revealed that the growth and electron transfer functions of EABs were predictive indicators for their electrochemical performance, with standardized path coefficients of 0.407 and 0.358, respectively. These findings enhance our understanding of EABs' response to Cd2+ shock and provide insights for improving their performance in heavy metal wastewater.

Omega-3 Polyunsaturated Fatty Acids Alleviate Intestinal Barrier Dysfunction in Obstructive Jaundice Rats.

Obstructive jaundice (OJ) can cause multiple pathophysiological consequences including intestinal barrier dysfunction. Omega-3 has been indicated to have a promising therapeutic effect on OJ. This study aimed to further investigate the functions of omega-3 on OJ-induced intestinal injury. A rat OJ model was established by bile duct ligation with or without omega-3 administration. ELISA was utilized for measuring serum levels of inflammatory cytokines. Hematoxylin-eosin staining and TUNEL staining were employed for detecting the morphological changes and cell apoptosis in rat intestine. Western blotting was utilized for evaluating expression of tight junction proteins in the intestinal tissues. Omgea-3 offset the reduction in body weight of OJ rats. Omega-3 alleviated inflammatory response, pathological damages and cell apoptosis in the intestine of OJ rats. Additionally, omega-3 enhanced levels of tight junction proteins in the intestinal tissues of OJ rats. Omega-3 ameliorates OJ-triggered impairment of intestinal barrier function in rats.

New insights from trio whole-exome sequencing in the children with kidney disease: A single-center retrospective cohort study.

BACKGROUND: Kidney disease of children markedly affects their health and development. Limited clinical data of early-stage kidney disease render a tremendous challenge for the accurate diagnosis. Trio whole-exome sequencing (Trio-WES) is emerging as a first-line diagnostic strategy in pediatric kidney disease, and shows important implications for the precision medicine strategies of children with kidney disease. METHODS: Trio-WES was performed in 133 Chinese children with kidney disease and their parents. The results for casual variants in genes known to cause kidney disease were analyzed. We further assessed the genetic diagnostic yield and the clinical implications of genetic testing. RESULTS: An overall diagnostic yield of 52.63% (70/133) was found, and the diagnostic rates ranged from 44.74% to 59.62% in different clinical phenotypes. The diagnostic yield of the three groups of simple proteinuria, renal insufficiency, and "other" was 50%, 50%, and 54.55%, respectively. Eight-seven diagnostic variants were identified in 70 probands with variants spanning 30 genes. The top 7 genes with diagnostic variants were COL4A5 (23, 26.44%), COL4A4 (13, 14.94%), ADCK4 (7, 8.05%), CLCN5 (3, 3.45%), ACE (3, 3.45%), PKD1 (3, 3.45%), and SLC12A3 (3, 3.45%), accounting for 63.22% of all variations in the cohort. CONCLUSIONS: The retrospective cohort study summarized the clinical utility of genetic testing in 133 probands, and expanded the phenotypic and genetic profiles of kidney disease in children. Trio-WES is an efficient diagnostic tool for children with kidney disease, which facilitates the clinical diagnosis and treatment. Our findings have important implications for the precise diagnosis of childhood nephropathy and may provide clinical guideline for disease management.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.

Overexpressing NeuroD1 reprograms Müller cells into various types of retinal neurons.

The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose- and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.

Performance of circulating methylated Septin9 gene DNA in diagnosis and recurrence monitoring of colorectal cancer in Western China.

BACKGROUND AND AIMS: Methylated Septin9 (mSEPT9) has been suggested for CRC detection. To assess the performance of mSEPT9 in Western China, we compared its diagnostic and recurrence monitoring values with fecal occult blood test (FOBT), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). MATERIAL AND METHODS: Overall 300 subjects including 209 CRC patients and 91 healthy subjects, who have performed mSEPT9, FOBT, CEA and CA19-9 tests, were involved. Sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the efficacy of each method. RESULTS: Plasma mSEPT9 demonstrated an AUC of 0.860, and a sensitivity of 76.4 % for CRC detection. The sensitivity of mSEPT9 was higher than FOBT, CEA and CA 19-9. Though mSEPT9 presented a larger or equal sensitivity for stage Ⅱ-IV CRCs, FOBT showed a better sensitivity for stage I CRCs. Logistical analysis showed the ones with positive mSEPT9, FOBT and CEA were more likely to have CRC (all P < 0.01). Then, the three biomarkers built the nomogram predicting the probability of having CRC. The sensitivity of mSEPT9 was also much higher than CEA for CRC recurrence monitoring. CONCLUSION: The mSEPT9 test performed better than traditional tests for CRC detection, and should be recommended for FOBT-positive ones or individuals who refuse FOBT.

An alternative asymmetric figure-of-eight single-layer suture technique for bowel anastomosis in an in vitro porcine model.

Anastomotic techniques are of vital importance in restoring gastrointestinal continuity after resection. An alternative asymmetric figure-of-eight single-layer suture anastomotic technique was introduced and its effects were evaluated in an in vitro porcine model. Twelve 15-cm grossly healthy small intestine segments from a porcine cadaver were harvested and randomly divided into asymmetric figure-of-eight single-layer suture (figure-of-eight suture) and single-layer interrupted suture technique (interrupted suture) groups (n = 6 in each group). The anastomosed bowel was infused with methylene blue solution to test anastomotic leakage. Anastomosis construction time, leakage, and suture material cost were recorded and analyzed statistically using Fisher's exact test and Student's t-test. One anastomotic leakage occurred (16.67%) in the figure-of-eight suture group, and two (33.33%) in the interrupted suture group (p > 0.9999). The anastomosis construction time was relatively short in the figure-of-eight suture group, but the difference did not reach a statistically significant level between the two groups. The mean number of suture knots and the cost of suture material in the figure-of-eight suture group were significantly decreased in comparison to the interrupted suture group (15.67 ± 3.30 vs. 22.17 ± 2.03, 167.11 ± 35.20 vs. 236.45 ± 21.70 CNY, p < 0.01, respectively). Our results suggested that the alternative asymmetric figure-of-eight suture technique was safe and economic for intestinal anastomosis. An in vivo experiment is required to elucidate the effects of this suture technique on the physiological anastomotic healing process.

A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases.

Background: The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods: Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results: 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion: HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02557490.

Early renal impairment is associated with in-hospital death of patients with COVID-19.

INTRODUCTION: Renal impairment is a common complication in coronavirus disease 2019 (COVID-19), although its prognostic significance remains unknown. OBJECTIVES: This study determines the impact of early renal impairment on the clinical outcome of COVID-19. METHODS: Patients diagnosed with COVID-19 and hospitalized in Xiaogan Central Hospital from 20 January to 29 February 2020 were retrospectively included and grouped into two cohorts (cohort with normal renal function and cohort with renal insufficiency) based on the renal function detected on admission. Records of clinical manifestation, laboratory findings and clinical outcome were collected and compared between these two cohorts. RESULTS: A total 543 COVID-19 patients were included. Among these patients, 70 patients developed early renal impairment, with an incidence of 12.89%. A significantly higher white blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatine (Cr), blood urine nitrogen (BUN) and brain natriuretic peptide (BNP) and a significantly lower blood platelet (PLT), lymphocyte count, prealbumin and albumin (ALB) were detected in the cohort with renal insufficiency (P < 0.05). Patients with early renal impairment were also associated with higher incidences of haematuria/proteinuria, higher incidences of mortality and prolonged hospitalization duration. The independent risk factors for in-hospital death included age >65 years old, complication of diabetes, renal impairment on admission (Cr > 73 µmol/L and eGFR < 60 ml/min 1.73 m2 ), WBC > 9.5 × 109 /L and ALB < 35 g/L. CONCLUSION: Early renal impairment is associated with higher risk of in-hospital death for patients with COVID-19. Risk stratification according to renal function can better guide the clinical management of COVID-19.

[Molecular Signatures of Dissolved Organic Matter in the Paihe River and Its Tributaries].

Dissolved organic matter (DOM) is an abundant and critical component of aquatic ecosystems, participating in many physicochemical and biogeochemical processes. The Paihe River is the only inflow river in the Jianghuai section of "Yangtze-Huaihe water diversion" clear water gallery project; however, its DOM molecular composition information and characteristics are still unclear. In this study, the molecular characterization of DOM in the Paihe River and Guangming Dayan River was determined using Orbitrap mass spectrometry. The Pearson's correlation and principal component analysis (PCA) were used to study the relationship between molecular composition information, characteristics, and sources of DOM in two rivers. The results showed that the molecular weight and oxygen content of DOM molecules in the Paihe River were relatively low; the molecular weight, aromaticity, and unsaturation of DOM molecules in the Guangming Dayan River were relatively high. From the element composition and compound composition of the two rivers' DOM, both rivers were mainly composed of CHO-compounds, lignin, and tannins derived from land plants, which indicates that both rivers were severely affected by terrestrial input. There were high percentages of CHOS, protein, and lipid compounds of DOM in the Paihe River. According to the results of the Pearson's correlation and PCA analyses, the DOM molecules of the Paihe River were also influenced by wastewater from sewage treatment plants, urbanization processes, and microbial activity. Molecular composition information and characteristics of DOM can provide a detailed reference to improve the theoretical support for the Paihe River clear water gallery project.

Inhibition of glioblastoma progression by Urolithin A in vitro and in vivo by regulating Sirt1-FOXO1 axis via ERK/AKT signaling pathways.

Glioblastoma (GBM) is the most universal and devastating primary intracranial neoplasm in the central nervous system. Urolithin A (UA) possesses many pharmacological and biological activities, but its function in GBM is not clear. CCK-8 and colony formation test were used to measure the anti-proliferative potency of UA against GBM cells. Flow cytometry was applied to evaluate cell cycle arrest and apoptosis of U251 and U118 MG cells upon UA incubation. Quantitative real-time PCR and western blotting were conducted to test the regulatory effect of UA on the expression of Sirt1 and FOXO1. Immunodeficient mice were implanted with GBM cells for in vivo validation of the anti-cancer effect of UA. We found UA repressed the proliferation, migration and invasion of glioblastoma cells, while also inhibiting the induction of colony formation ability and epithelial to mesenchymal transition (EMT) in a time- or dose-dependent manner. The does-dependent relationship of UA inducing the cell cycle arrest and apoptosis of glioblastoma cells was identified. Furthermore, UA could enhance the expression levels of Sirt1 and FOXO1 and the knockdown of Sirt1 blocked the inhibitory effects of UA on the proliferation and migration of glioblastoma cells and correspondingly modified the expression level of FOXO1. Overexpression of Sirt1 restored the despaired inhibitory effect of UA induced by Sirt1 knockout on the proliferation and migration of glioblastoma cells. In animal experiments, UA decreased the tumor size and weight of glioblastoma in xenograft nude mice and promoted the expression of Sirt1 and FOXO1 in transplanted tumors. Our findings presented in this study indicate that UA exerts a repressive effect on glioblastoma cells in vivo and in vitro by regulating the Sirt1-FOXO1 axis via the ERK and AKT pathways, indicating that UA is a new novel therapeutic candidate for the treatment of glioblastoma.

Efficacy of small-dose ganciclovir on cytomegalovirus infections in children and its effects on liver function and miR-UL112-3p expression.

The aim of the study was to explore the efficacy of small-dose ganciclovir on cytomegalovirus infections as well as its effects on the liver function and miR-UL112-3p of children. A total of 141 children infected with cytomegalovirus admitted to the Affiliated Hospital of Weifang Medical University from May 2015 to August 2017 were enrolled, of which 74 children were treated with small-dose ganciclovir as an observation group (Obs group), and the rest were treated with conventional-dose ganciclovir as a control group (Con group). The two groups were compared in efficacy after treatment, changes of liver function indexes [total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] and miR-UL112-3p before and after treatment, and adverse reactions after treatment. A receiver operating characteristic (ROC) curve was drawn to analyze the value of miR-UL112-3p in predicating efficacy on cytomegalovirus infections in children, and Pearson's correlation analysis was carried out to analyze the correlation between miR-UL112-3p expression and TB, ALT and AST. The MV-DNA level between the two groups after treatment was compared. The two groups showed no significant difference in efficacy and adverse reactions (both P>0.05), and before treatment, there was also no significant difference between the two groups in miR-UL112-3p, TB, ALT, and AST, while after treatment, both groups showed lower levels of miR-UL112-3p, TB, ALT, and AST, and the Obs group showed significantly lower levels thereof than the Con group (all P<0.05). In addition, the area under the curve (AUC), specificity, and sensitivity of miR-UL112-3p in the ROC curve of the Obs group were 0.866, 73.77 and 84.62%, respectively, while the AUC, specificity, and sensitivity of the ROC of the Con group were 0.837, 75.44, and 90.00%, respectively. Furthermore, miR-UL112-3p was positively correlated with TB, ALT, and AST, respectively. The CMV-DNA level in the Obs group was lower than that in the Con group, but the difference was not significant, and the level of CMV-DNA was positively correlated with that of miR-UL112-3p. In conclusion, small-dose ganciclovir can better improve the liver function of the children, and downregulate miR-UL112-3p in them. The AUC, specificity, and sensitivity of miR-UL112-3p for predicting the efficacy of small-dose ganciclovir were 0.866, 73.77 and 84.62%, respectively, and the AUC, specificity, and sensitivityfor predicting the efficacy of conventional-dose ganciclovir were 0.837, 75.44 and 90.00%, respectively.

Evaluation of IGRT-Induced Imaging Doses and Secondary Cancer Risk for SBRT Early Lung Cancer Patients In Silico Study.

OBJECTIVES: This study performed dosimetry studies and secondary cancer risk assessments on using electronic portal imaging device (EPID) and cone beam computed tomography (CBCT) as image guided tools for the early lung cancer patients treated with SBRT. METHODS: The imaging doses from MV-EPID and kV-CBCT of the Edge accelerator were retrospectively added to sixty-one SBRT treatment plans of early lung cancer patients. The MV-EPID imaging dose (6MV Photon beam) was calculated in Pinnacle TPS, and the kV-CBCT imaging dose was simulated and calculated by modeling of the kV energy beam in TPS using Pinnacle automatic modeling program. Three types of plans, namely PlanEPID, PlanCBCT and Planorigin, were generated with incorporating doses of EPID, CBCT and no imaging, respectively, for analysis. The effects of imaging doses on dose-volume-histogram (DVH) and plan quality were analyzed, and the excess absolute risk (EAR) of secondary cancer for ipsilateral lung was evaluated. RESULTS: The regions that received less than 50 cGy were significantly impacted by the imaging doses, while the isodose lines greater than 1000 cGy were barely changed. The DVH values of ipsilateral lung increased the most in PlanEPID, followed by PlanCBCT. Compared to Planorigin on the average, the estimated EAR of ipsilateral lung in PlanEPID increased by 3.43%, while the corresponding EAR increase in PlanCBCT was much smaller (about 0.4%). Considering only the contribution of the imaging dose, the EAR values for the ipsilateral lung due to the MV-EPID dose in 5 years,10 years and 15 years were 1.49 cases, 2.09 cases and 2.88 cases per 104PY respectively, and those due to the kV-CBCT dose were about 9 times lower, correspondingly. CONCLUSIONS: The imaging doses produced by MV-EPID and kV-CBCT had little effects on the target dose coverage. The secondary cancer risk caused by MV-EPID dose is more than 8.5 times that of kV-CBCT.

Individualized Fraction Regimen of SBRT Patients With Non-Small Cell Lung Cancer Based on Uncomplicated and Cancer-Free Control Probability.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) currently adopts non-discriminative prescription regimen. This study attempts to investigate an individualized fraction regimen (IFR) method for SBRT patients with non-small cell lung cancer (NSCLC) based on Uncomplicated and Cancer-free Control Probability (UCFCP). METHODS: Twenty patients with NSCLC were retrospectively prescribed with 40 regimens, ranging from 8Gy×5f to 12Gy×5f in step of 0.1 Gy. Taking into consideration of the age and the BMI index of each patient as well, the tumor control probability (TCP), the normal tissue complication probability (NTCP) of the total lung, chest wall and rib, and the secondary cancer probability (SCP) of the total lung were calculated for each plan of the patients. For the 40 regimens, the UCFCP was calculated and the maximum value of UCFCP was the IFR of the specified patient. Besides, IFR of UCP approach which only took account of the TCP and NTCP was also derived and to be compared with the IFR based on the UCFCP method. RESULTS: For all the patients, the UCFCP value showed a bell-shaped trend with the change of prescription dose. Among the 20 patients, the IFRs of 16 patients were different from the original fixed regimen. Of the 16 patients, the IFR of 5 patients exhibited slight changes between UCP and UCFCP methods. CONCLUSION: The method based on the maximum value of UCFCP function may be helpful to provide IFR for specific SBRT patients with NSCLC, differentiating the patient specific characteristics such as anatomical structures and locations.

Photophysical properties and stimuli-responsive crystal-state luminescence switching of morpholine-modified naphthalic anhydride derivative.

Stimuli-response organic solid-state luminescence switching materials are attracting increasing interest due to their smart photophysical properties. In this study, a morpholine-modified naphthalic anhydride derivative, 4-(4-morpholinyl)naphthalic anhydride (MBC), was synthesized and studied. Its two crystal polymorphs, MBC-G and MBC-O, were obtained under different crystallization conditions. These two distinct crystals show significantly different solid-state luminescence behaviors: a green emission at 535 nm for MBC-G, and an orange emission at 572 nm for MBC-O. Upon fiercely grinding the MBC-G crystal or melting and then quickly cooling it, a phase transition occurs from MBC-G to MBC-O, accompanied by a fluorescence change from green to orange. The reverse transformation from MBC-O to MBC-G can be achieved by recrystallization. The X-ray single crystal structures show that the green emission should be attributed to molecular J-aggregation in the crystal packing, and the orange emission may originate from molecular H-aggregation. This switchable color nature gives MBC the promising candidate for potential smart anti-counterfeiting and light-emitting materials.

Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice.

Inhibitor of DNA binding 2 (Id2) can promote axonal regeneration after injury of the central nervous system. However, whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown. In this study, we established a mouse model of bilateral sciatic nerve crush injury. Two weeks before injury, AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord. Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve, and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury, arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle. By 1 month after injury, extensive neuromuscular reinnervation occurred. In addition, the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered, and their latency was shortened. These findings suggest that Id2 can accelerate axonal regeneration, promote neuromuscular reinnervation, and enhance functional improvement following sciatic nerve injury. Therefore, elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury. The study was approved by the Experimental Animal Ethics Committee of Jinan University (approval No. 20160302003) on March 2, 2016.

Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment.

To select the most efficient chemical to induce apoptosis in leukemia cells, a multidrug screen was applied on bone marrow mononuclear cells from chronic myeloid leukemia (CML) patients. Oprozomib (Cpd 21) was chosen for the subsequent experiments. The isobaric tags for relative and absolute quantitation (iTRAQ) was then performed to identify the responsible pathway relative to apoptosis and the results showed that endoplasmic reticulum (ER) chaperones were upregulated. Apoptosis was attributed to a joint effect of calcium leakage andPERK and IRE1α phosphorylation. The PERK branch was responsible for the first wave of cell death that occurred within 24 hours. The later wave of apoptosis was mediated by IRE1α, which transmit apoptotic signals through the ASK-JNK-BIM axis. Release of Ca2+ from ER into cytosol resulted in activation of calpain, which, in turn, cleaved caspase-12. Our data also explained the selective killing effects of oprozomib on CML cells, which relied on proteasome activity. The present study demonstrated that prolonged inhibition of proteasome to trigger unfolded protein response could be an alternative strategy for treating CML in light of tyrosine kinase inhibitors resistance.